New possibilities of treatment for panic attacks in elderly patients: escitalopram versus citalopram

PURPOSE: Panic attacks may represent additional therapeutic problems in the elderly. The utility of citalopram in panic attacks has been widely investigated. Here, we compare the efficacy and safety of citalopram, with its S-enantiomer escitalopram at half dosage as to citalopram, in elderly patients who have panic attacks. METHODS: This was an open community-based study. Forty patients who have panic attacks, according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, were enrolled. Fifty percent of the patients were assigned for 8 weeks' treatment with escitalopram, and the remaining 50% were assigned to treatment with citalopram. The primary outcome measure was the weekly rate of panic attacks. The secondary outcome measures were the Hamilton scale for anxiety and depression and the Cooper Disability Scale. Analysis of variance by repeated measures was applied to calculate differences between groups. RESULTS: A similar decrease in weekly rate of panic attacks, in the scores of Hamilton Scale for anxiety and depression and in the Cooper Disability Scale scores, was observed in both groups after 8 weeks, but a significant variation of outcome measures from baseline was observed already after 2 weeks in the escitalopram group (P < 0.001) and only after 4 weeks in the citalopram group (P < 0.01). CONCLUSIONS: Escitalopram could be considered among the drugs of first choice in elderly patients with panic attacks because of its good efficacy and safety and for the advantage of reducing the total dose and of a more rapid onset of action as compared with citalopram, although further studies are needed to confirm these results.     

Efficacy of imipramine in psychotic versus nonpsychotic depression

The purpose of the present study is to compare the efficacy of imipramine in the treatment of psychotic versus nonpsychotic depression. Previous studies report varying results of monotherapy with antidepressants in psychotic depression. Because psychotic depression is seriously underinvestigated, performing a post hoc analysis of randomized clinical trials consisting of both psychotic and nonpsychotic depressed patients may contribute to the discussion on the optimal treatment of depressed patients with mood-congruent psychotic features. A total of 112 patients diagnosed with major depression (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) (40 with psychotic depression and 82 without psychotic features) received treatment with imipramine for 6 weeks after a washout period of 7 days. Imipramine doses were adjusted to attain a predefined fixed plasma level. Treatment response was assessed with the Hamilton Rating Scale for Depression (HAM-D). A logistic regression analysis showed a significantly larger reduction in HAM-D score in the sample with psychotic features compared with the nonpsychotic sample (regression coefficient, -3.47; SE, 1.7; P = 0.04). According to the primary outcome criterion, that is, the change in HAM-D score, imipramine was significantly more effective in the sample with psychotic depression compared with the nonpsychotic depressed patients. The contradiction between our results and those of several previous studies may be due to the fixed plasma level dosing of imipramine refraining from concurrent psychotropic medication or limiting our patient sample to patients with mood-congruent psychotic features.     

The efficacy of divalproex sodium in the treatment of agitation associated with major depression

BACKGROUND: Agitation is both a feature of major depression and a common side effect of antidepressant treatment. Depressive agitation correlates with overall severity of illness and suicide risk, whereas treatment-emergent agitation may contribute to early discontinuation of pharmacotherapy. Thus, agitation merits investigation as a treatment target in clinical depression. METHODS: In this study, adults with major depression were evaluated for change in agitation and other mood symptoms during adjunctive treatment with divalproex sodium. Twelve patients on antidepressants, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression, were given low doses of divalproex sodium and evaluated repeatedly for symptoms of depression, anxiety, and agitation. Agitation severity was evaluated using the Overt Agitation Severity Scale and the Stanford Scale for Agitation Symptoms. Mood symptoms were assessed with the Hamilton Anxiety and the Hamilton Depression Rating Scales. RESULTS: Nine of 12 patients completed 4 weeks of treatment. All agitation scores decreased sharply, whereas depression (Hamilton Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale) symptoms decreased only modestly. Decreased agitation was not merely a function of decreases on the Hamilton Depression or Hamilton Anxiety Rating Scales. Relatively low doses of divalproex sodium appear to be useful in the treatment of agitation associated with major depression. CONCLUSIONS: The observation that decreases in agitation were not simply an artifact of overall change in depressive or anxiety symptoms is in keeping with the previous clinical impression that divalproex sodium has a specific effect on depressive agitation. Controlled clinical trials are needed to fully evaluate the utility and symptom specificity of divalproex sodium in depression.     

Does fluoxetine have any effect on the cognition of patients with mild cognitive impairment? A double-blind, placebo-controlled, clinical trial

OBJECTIVES: Mild cognitive impairment (MCI) may be a prodromal state for Alzheimer disease. Recent research suggest a role for other neuronal systems such as monoaminergic hypofunction beside cholinergic dysfunction in age-related cognitive decline. In several studies, selective serotonin reuptake inhibitors demonstrated promotion of neurogenesis in the hippocampus. In this study, the effects of fluoxetine, a selective serotonin reuptake inhibitor, on memory and cognition of patients with mild cognitive impairment has been studied. METHOD: Fifty-eight nondepressed patients with MCI were randomly assigned to take fluoxetine or placebo. The patients were administered the Structured Clinical Interview for DSM-IV (Diagnosis and Statistical Manual for Mental Disorders, Fourth Edition) Disorders, the Mini-Mental Status Examination (MMSE), subtests from the Persian standardized Wechsler Memory Scale III (WMS-III) preintervention. Forty-four patients completed the 8-week trial. Treatment response was defined as improvement in the scores of MMSE, subtests of WMS-III, and Clinical Global Impression. RESULT: The patients in the fluoxetine group showed improvement in MMSE and immediate and delayed logical memory scores of WMS-III. The placebo group had no significant changes in the cognitive measurements. CONCLUSION: Fluoxetine enhanced memory and cognition in the patients. This was consistent with previous studies that emphasized the role of fluoxetine in improving memory and promoting neurogenesis in the hippocampus. However, this is a preliminary study with small sample size, and larger double-blind placebo-controlled studies are needed to confirm these findings.     

Efficacy of quetiapine monotherapy in bipolar I and II depression: a double-blind, placebo-controlled study (the BOLDER II study)

This study evaluated the efficacy and tolerability of quetiapine monotherapy for depressive episodes in patients with bipolar I or II disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) who were randomized to 8 weeks of double-blind treatment with quetiapine (300 or 600 mg/d; once daily, evening dosing) or placebo. Patients were assessed weekly using the Montgomery-Asberg Depression Rating Scale (MADRS) and Hamilton Depression Rating Scale (HAM-D). The primary end point was change in MADRS total score from baseline to Week 8 (analysis of covariance/last-observation-carried-forward analysis). Of 509 patients randomized, 59% completed the study. Improvements from baseline in mean MADRS total scores were significantly greater with quetiapine 300 and 600 mg/d than with placebo from first evaluation (Week 1) through Week 8 (both P 相似文献   

Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial

BACKGROUND: Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients. METHODS: Under double-blind conditions, 93 hospitalized patients older than 59 years, who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for a major depressive episode, were randomly assigned to receive sertraline (150 mg daily) or fluvoxamine (200 mg daily) for 7 weeks. The clinical response was defined as a reduction on the Hamilton Rating Scale for Depression score to 8 or below. RESULTS: At study completion, the response rates were 55.6% (25/45) and 71.8% (28/39) for sertraline and fluvoxamine, respectively. No significant difference in final response rates was found between the 2 treatment groups (P = 0.12). A repeated-measures analysis of variance on Hamilton Rating Scale for Depression scores revealed a significantly different decrease of depressive symptoms between the 2 treatment groups, favoring fluvoxamine (P = 0.007). The overall safety profile of sertraline and fluvoxamine was favorable with no differences between the 2 drugs. CONCLUSION: The results of this double-blind trial show that sertraline and fluvoxamine may be effective compounds in the treatment of elderly depression with the latter showing some advantage in terms of speed of response. These findings warrant further replication in placebo-controlled studies.     

Mood disorders affect drug treatment success of drug-dependent pregnant women

This study examined the impact of co-occurring Axis I disorders on drug treatment outcomes of drug-dependent pregnant women. Participants (N = 106) were women who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for opioid dependence and were receiving methadone. Based on DSM-IV Axis I criteria, participants were categorized into three groups: (1) absence of mood/anxiety disorder (ND, n = 29), (2) primary mood disorder (MD, n = 39), or (3) primary anxiety disorder (AD, n = 38). Demographically, the groups were similar. The MD group was significantly more likely to be positive for drugs while in treatment compared with both the ND and AD groups. The MD and AD groups had more psychosocial impairment and higher incidence of suicidal ideation compared with the ND group. Interestingly, the AD group spent more days in treatment compared with the ND or MD group. These findings highlight the need to treat co-occurring Axis I disorders, particularly given the higher relapse risk for those with mood disorders.     

Impact of Central Nervous System Stimulant Medication Use on Growth in Pediatric Populations with Attention-Deficit/Hyperactivity Disorder: A Review

Central nervous system stimulants are a commonly used first-line treatment option for attention-deficit/hyperactivity disorder (ADHD). Stimulants are generally well tolerated, with anorexia and insomnia the most common adverse effects. However, there are some concerns with long-term use of stimulants, such as potential growth delay. Historically, data regarding this long-term adverse effect have been conflicting. In this article, we review the newer data surrounding the effects of central nervous system stimulants on growth parameters in children with ADHD. We conducted a literature search of the PubMed database; only articles using ADHD criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, were included to ensure the most up-to-date review of literature. Nine articles were identified for relevance and quality and are discussed in this review, describing clinical observations of height and weight of adolescent or pediatric patients receiving stimulant medications for ADHD therapy. In summary, this review points toward potential associations between duration of treatment and higher doses of stimulants with decreased weight and body mass index. Furthermore, this review demonstrates that evidence is still conflicting regarding the relationship between stimulant use and significant height decreases. Future studies with higher quality of evidence are needed to observe this potential adverse effect of stimulants in children and adolescents.     

Venlafaxine for the treatment of depressive episode during the course of schizophrenia

The emergence of depression in the course of schizophrenia is common and arouses much interest and therapeutic concern. It has been associated with a less favorable prognosis and increased incidence of suicide. However, relatively few treatment studies have been performed in this area. The use of a combination of antidepressants and antipsychotic agents is controversial. We report an open-label study carried out to evaluate the efficacy of the addition of venlafaxine in schizophrenia patients treated with antipsychotics and diagnosed with concurrent depressive episode (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria). Patients (N = 19) who did not show spontaneous improvement after 4 weeks were assigned to a 6-week trial with add-on venlafaxine. Patients were evaluated at a 1-week interval with the Hamilton Depressive Rating Scale, the Positive and Negative Syndrome Scale, and the Clinical Global Impression Scale. All 19 patients had completed the 6-week trial. Fourteen patients (74%) showed significant improvement measured with Hamilton Depressive Rating Scale and Clinical Global Impression Scale. The mean venlafaxine dose was 146 mg/d (range: 75 to 225 mg/d). In most patients, there was a parallel decrease in psychotic symptoms. We conclude that venlafaxine may have a role in the treatment of depression in patients with schizophrenia without causing exacerbation of psychosis.     

Imipramine and buspirone in patients with panic disorder who are discontinuing long-term benzodiazepine therapy

Pretreatment with imipramine, buspirone, or placebo was compared in 40 patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria for panic disorder and in patients who were discontinuing long-term benzodiazepine use. The average duration of benzodiazepine use was 75 +/- 64 months, and the average benzodiazepine intake expressed as diazepam equivalents was 25.7 +/- 19 mg/d. We hypothesized that pretreatment with either imipramine or buspirone, in contrast to pretreatment with placebo, would lead to a significant decrease of symptoms of anxiety and depression before tapering benzodiazepines, thus making the taper process easier to complete. All 3 treatments (imipramine, buspirone, and placebo) caused a reduction in anxiety and depression symptoms as measured by changes in the Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. Neither discontinuation severity nor taper-free status 12 weeks posttaper differed between the 3 treatment groups.     

Effects of PRX-00023, a novel, selective serotonin 1A receptor agonist on measures of anxiety and depression in generalized anxiety disorder: results of a double-blind, placebo-controlled trial

PRX-00023, a serotonin 1A receptor agonist, was designed to provide high potency and selectivity for its target. To assess the possible therapeutic utility in anxiety, a randomized, double-blind, placebo-controlled trial was conducted in 311 subjects who met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, for generalized anxiety disorder. All subjects underwent a 1-week placebo run-in and were randomized to receive once-daily capsules containing either PRX-00023 (80 mg/d) or placebo for an additional 8 weeks. The primary outcome measure was the Hamilton Anxiety Scale (HAM-A). The Montgomery-Asberg Depression Rating Scale was used as a secondary endpoint to measure depressive symptoms. Statistical testing was performed with analysis of covariance, between baseline and week 8, with baseline values as a covariate. The anxiolytic effect of PRX-00023, compared with placebo, showed trends across all anxiolytic measures but failed to reach significance on the primary endpoint (HAM-A total score). Among the components of the HAM-A total score, the anxious mood item was significantly different from placebo in the PRX-00023-treated group (-1.015 vs -0.748; P = 0.02). The scores of the Montgomery-Asberg Depression Rating Scale were significantly improved compared with placebo at week 8 (-4.5 vs -1.6; P = 0.0094 in the last observation carried forward analysis). PRX-00023 was well tolerated; of note, there were no drug-related serious adverse events, and more patients discontinued due to adverse events in the placebo group (2.9%) than in the PRX-00023 group (1.4%). The most common adverse event was headache, observed in 15.7% and 10.9% of PRX-00023- and placebo-treated patients, respectively. Furthermore, there was no evidence of impaired sexual function, as measured by the Massachusetts General Hospital Sexual Function Scale. Collectively, these results support further clinical investigation of higher doses of PRX-00023 in anxiety and depression.     

P3a amplitude predicts successful treatment program completion in substance-dependent individuals

This study examined P3a amplitude as a direct predictor of treatment success for substance dependence. Participants were 35 adults (27 men, 8 women) undergoing treatment for substance dependence at an urban residential treatment facility between October 2005 and July 2007. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria were used to confirm substance dependence. P3a amplitude was significantly smaller for those who dropped out of treatment. Discriminant function analysis confirmed that P3a amplitude was a robust predictor of treatment completion, more sensitive than other measures including substance abuse severity. Implications for the interpretation of P3a amplitude as an index of executive function are discussed.     

Intravenous augmentative citalopram versus clomipramine in partial/nonresponder depressed patients: a short-term, low dose, randomized, placebo-controlled study

The aim of the present study was to evaluate the efficacy of short-term low-dose intravenous augmentative citalopram (10 mg/d) versus clomipramine (25 mg/d) versus placebo in a sample of patients with MDE and partial or no response to selective serotonin reuptake inhibitors (SSRIs). Fifty-four patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, MDE and partial or no response to SSRIs per os (21-item Hamilton Depression Rating Scale [HAM-D21] score reduction, <50% or < or =25%, respectively, compared with pretreatment scores) were selected and randomized to citalopram (n = 18), clomipramine (n = 18), or placebo (n = 18) intravenous augmentation. The augmentation regimen lasted 5 days during which patients were maintained on their previous treatment with oral SSRIs. Analyses of variance with repeated measures on HAM-D(21), collected daily in blind-raters design, were performed to detect any change of depressive symptoms between the 3 groups. In addition, the number of responders and remitters was computed in the 3 groups of treatment. At end point, a significant treatment effect (F= 4.57; P = 0.015) and time-by-treatment effect (F = 11.22; P < 0.0001) were found on HAM-D21 total scores in favor of citalopram and clomipramine versus placebo, with a superiority of citalopram over clomipramine on overall symptoms (P = 0.05) as well as on anxiety-somatization symptoms (P = 0.027). The number of responders was significantly superior in the active treatment groups versus the placebo group ([chi](2)(2) = 16.36; P < 0.0001). The same result was found, considering the number of remitters ([chi](2)(2) = 13.50; P < 0.0001). Present findings suggest that both clomipramine and citalopram intravenous augmentation at low doses and for a short period are well tolerated and superior to placebo in major depressives with partial or no response to oral SSRIs with a possible superiority of citalopram over clomipramine with regard to anxiety-somatization symptoms. The lack of double-blind conditions and the limited sample size may limit the confidence in the reported results, and larger randomized controlled trials are warranted to confirm the present findings.     

The resistance to depressive relapse in menopausal women undergoing tryptophan depletion: preliminary findings

Changes in neuroendocrine function may predispose menopausal women to psychological disturbances characterized by depressed mood, anxiety, irritability, fatigue, insomnia, forgetfulness and decline in libido. The acute tryptophan depletion paradigm was employed to examine the serotonergic contribution to mood and cognitive function in menopausal women who were within 4 weeks of recovery from an episode of major depression. Menopausal women whose depression was responsive to treatment with oestradiol, the selective serotonin reuptake inhibitor fluoxetine, or a combination of both treatments underwent assessment of mood and verbal memory on active tryptophan depLetion and sham depletion test days. Although performance on the delayed paragraph recall subtest of the Wechsler Memory Scale was impaired by tryptophan depletion, no subjects experienced a relapse of depression or a significant worsening of mood. Results from this pilot study indicate that menopausal women who have recently recovered from a major depressive episode do not experience a worsening of mood with acute tryptophan depletion, despite the existence in this sample of some known risk factors for depressive relapse as a result of these procedures. While preliminary, the results suggest that serotonin may be less critical to the pathogenesis of depression during the menopause.     

Naltrexone and disulfiram in patients with alcohol dependence and current depression

OBJECTIVE: Although disulfiram and naltrexone have been approved by the Food and Drug Administration for the treatment of alcoholism, no medications have been approved for individuals with alcohol dependence and comorbid psychiatric disorders. In particular, the effect of these medications on alcohol use outcomes and on specific psychiatric symptoms is still unknown in patients with the most common co-occurring disorder, major depression. METHOD: Two hundred fifty-four patients with a major Axis I psychiatric disorder and comorbid alcohol dependence were treated for 12 weeks in an outpatient medication study conducted at 3 Veterans Administration outpatient clinics. Randomization included (1) open randomization to disulfiram or no disulfiram, and (2) double-blind randomization to naltrexone or placebo. This resulted in 4 groups: (1) naltrexone alone, (2) placebo alone, (3) disulfiram and naltrexone, and (4) disulfiram and placebo. Primary outcomes were measures of alcohol use. Secondary outcomes included psychiatric symptoms assessed by the Hamilton Depression Rating Scale, alcohol craving, gamma-glutamyltransferase levels, and adverse events. RESULTS: One hundred thirty-nine subjects (54.7%) met the current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for major depression. There was no relationship between the diagnosis of depression and medication treatment on alcohol use outcomes, psychiatric symptoms, or the reporting of side effects for these medications. There was a significant interaction between diagnosis, medication group, and craving, where subjects with depression on disulfram reported lower craving over time than subjects with depression on naltrexone. CONCLUSIONS: The results suggest that disulfiram and naltrexone are safe pharmacotherapeutic agents for dually diagnosed individuals with depression for the treatment of alcohol use disorders.     

Bupropion in the treatment of pathological gambling: a randomized, double-blind, placebo-controlled, flexible-dose study

We tested the efficacy of bupropion in the treatment of persons with pathological gambling (PG). Nondepressed, healthy subjects with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition PG were randomly assigned to placebo or flexibly dosed bupropion in a 12-week double-blind trial. Outcome measures included the Yale-Brown Obsessive-Compulsive Scale modified for PG, the Gambling Severity Assessment Scale, the Clinical Global Impression Improvement and Severity Scales, the Global Assessment Scale, the Timeline Follow Back, the Attention-Deficit/Hyperactivity Disorder Rating Scale, and the Sheehan Disability Scale. Thirty-nine subjects (28 men, 11 women) were randomized to bupropion (n = 18) or placebo (n = 21). The 2 groups were similar on demographic and clinical measures. There were few differences between the treatment groups on any primary or secondary outcome measure, although subjects in each cell experienced significant improvement. Of subjects with at least 1 postrandomization visit, 35.7% of bupropion and 47.1% of placebo recipients experienced "much" or "very much" improvement on the Clinical Global Impression Improvement Scale. The trial was complicated by a high noncompletion rate (43.6%). Bupropion was well tolerated. Bupropion and placebo recipients did equally well in a short-term trial, with improvement seen as early as the first week of treatment. The high placebo response rate and the high noncompletion rate each reflect the challenge inherent in treating persons with PG.     

Amantadine for weight gain associated with olanzapine treatment.

Patients with schizophrenia (Sch), schizoaffective, schizophreniform, or bipolar (BP) I disorders [Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV)]; not manic or acutely psychotic [Brief Psychiatric Rating Scale (BPRS) total score < or =45]; treated with olanzapine for 1-24 months; and who had gained > or =5% of their initial body weight were examined to determine whether amantadine could attenuate weight gain or promote weight loss. Olanzapine (Olz; 5-20 mg/day) was co-administered with double-blind treatment of 100-300 mg/day amantadine (Olz+Amt, n=60) or placebo (Olz+Plc, n=65). Visit-wise analysis of weight showed that weight change from baseline [last-observation-carried-forward (LOCF)] in the Olz+Amt group was significantly different from the Olz+Plc group at weeks 8 (P=0.042), 12 (P=0.029), and 16 (primary endpoint, mean+/-S.D.: -0.19+/-4.58 versus 1.28+/-4.26 kg, P=0.045). Mean BPRS total score, positive subscale, and anxiety-depression scores improved comparably in both groups, and Montgomery-Asberg Depression Rating Scale (MADRS) total score improved in the Olz+Amt group. Overall, amantadine was safe, was well tolerated, and attenuated weight gain or promoted weight loss in some patients who had gained weight during olanzapine therapy.     

Diagnosis and assessment of alcohol use disorders among adolescents

The diagnostic criteria for alcohol use disorders (AUDs) (i.e., alcohol abuse and alcohol dependence) as defined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) were developed largely from research and clinical experience with adults. Little is known about the validity of these criteria when applied to adolescents. Recent epidemiological and clinical studies of AUDs and their symptoms among adolescents have indicated that the DSM-IV criteria have significant limitations when applied to this age group. Diagnostic interviews and screening tools for adolescent AUDs are discussed. Numerous instruments are available that have shown moderate-to-high reliability and validity in assessing AUDs among adolescents.     

Add-on mirtazapine enhances effects on cognition in schizophrenic patients under stabilized treatment with clozapine

The development of therapeutic strategies for cognitive dysfunction remains one of the primary goals in the treatment of schizophrenia. The pharmacodynamic profile of mirtazapine, an antidepressant that enhances noradrenergic and serotonergic transmission, is based on a presynaptic alpha2 antagonism and postsynaptic 5-HT2 and 5-HT3 antagonism. Mirtazapine shares some pharmacological similarities with that of clozapine. This 8-week open label trial aimed to discover whether the addition of 30 mg mirtazapine could potentiate the effects on cognition of an ongoing stabilized clozapine therapy in 15 persons who met the criteria for chronic schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000). Mirtazapine adjunction was well tolerated and induced a significant improvement in cognitive performance, as measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; Randolph, 1998) total score and by the subscales for immediate and delayed memory (p<.01). Since Hamilton Depression Rating Scale (HAM-D; Hamilton, 1967), Brief Psychiatric Rating Scale (BPRS; Overall & Gorham, 1962), and Scale for the Assessment of Negative Symptoms (SANS; Andreasen, 1989) scores at Week 8 did not show significant differences from baseline, the improvements in the effects of clozapine on cognition observed after the addition of mirtazapine seemed to be a direct rather than an indirect action of this drug (e.g., via mood or other psychopathological symptoms). These findings suggest a potential role for mirtazapine as a useful strategy to augment the efficacy of clozapine in the treatment of cognitive dysfunctions in chronic schizophrenia.